In the general population, hypertension is detrimental and clearly leads to adverse cardiovascular events. Despite high cardiovascular morbidity and mortality in end-stage renal disease (ESRD) patients, the relationship between hypertension and cardiovascular outcomes in ESRD patients is unclear. Thus, the principal investigator's goal is to establish a career as an independent clinical scientist with the broad objectives of understanding the pathophysiologic mechanisms associated with blood pressure in ESRD patients and to identify how to manage blood pressure in ESRD patients to improve cardiovascular outcomes. Specifically this research aims: 1) To demonstrate in a national US hemodialysis cohort (USRDS) that blood pressure elevations occurring from pre to post hemodialysis (deltaSBP) are associated with increased cardiovascular events, thus identifying a high-risk cohort of patients who may benefit from BP reduction. 2) To demonstrate in a cross sectional case-control cohort analysis of 40 hemodialysis patients that blood pressure elevations with hemodialysis are associated with decreased endothelial progenitor cells and impaired flow mediated dilation defining endothelial cell dysfunction, a novel mechanistic marker in the causal pathway for detrimental cardiovascular outcomes. 3) To demonstrate that lowering blood pressure with carvedilol in a cohort of 20 hemodialysis subjects with paradoxical rises in BP with hemodialysis can improve endothelial cell dysfunction as a mechanistic marker for improving cardiovascular outcomes. This career development award will not only identify pathophysiologic mechanisms associated with high blood pressure in dialysis patients but also seeks to identify whether lowering blood pressure in high-risk hypertensive dialysis patients can modify the underlying mechanism associated with increased cardiovascular risk: endothelial cell dysfunction. With the resources of Duke University, Duke Clinical Research Center, The Stedman Center for Research, established successful mentors and basic science collaborators, this award will provide Dr. Inrig with the necessary training and tools to support her transition to an independent clinical investigator. (End of Abstract) [unreadable] [unreadable]